P603: INFECTIONS BEFORE AND DURING IMMUNOGLOBULIN REPLACEMENT THERAPY IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA.
Authors: Christian Brieghel, Esben Munk Packness, Casper Møller Frederiksen, Carsten Niemann
Journal: HemaSphere (2023)

Background: Infections are the leading cause of death in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). To prevent infections, immunoglobulin replacement therapy (IgRT) is recommended in patients with both low IgG levels and at least two severe infections within a year. However, updated evidence for the efficacy of IgRT is warranted. Aims: To investigate the antimicrobial use in CLL/SLL before and during IgRT. Methods: We used the Danish Lymphoid Cancer Research (DALY-CARE) database to retrieve information on IgG levels, antimicrobial prescriptions, in-hospital antimicrobials, and vital values for all patients with CLL/SLL in electronic health records receiving IgRT in eastern Denmark. Infections were defined as grade 1-2 if treated with prescription drugs only and grade 3-4 if treated in-hospital with antimicrobials. Further, grade 3-4 infections with a maximum quick sequential organ failure assessment (qSOFA) score of 0-1 and 2-3 were divided into grade 3 and 4 infections, respectively. Antimicrobials prescribed within 14 days of one-another and in-hospital antimicrobials discontinued for less than 7 days were defined as 1 infectious event. To describe the antimicrobial use before and during IgRT, we calculated quarterly proportions of patients with grade 1-2, 3, and 4 infections. Results: Among 4,419 patients with CLL/SLL, we identified 239 receiving IgRT (187 CLL and 52 SLL). At diagnosis, the median age was 63 (IQR 57-69) years as compared to 72 (IQR 66-77) years at time of IgRT initiation. IgG levels increased significantly from 4.2 g/L (IQR 2.6-6.2) before IgRT to 6.9 g/L (IQR 5.3-9.3) after IgRT (P<0.0001). With a median follow-up of 5.6 years, we retrieved 1939 antimicrobial prescriptions filled for 140/239 (58.6%) patients and 29,157 in-hospital antimicrobial doses administered in 224/239 (93.7%) hospitalized patients: 15 (6.3%) patients had no history of antimicrobial use. We recorded 2458 infectious events among the 224 patients with antimicrobial use: 1472 (59.9%) occurred in 138 patients with grade 1-2 infections, 879 (35.8%) occurred in 198 patients with grade 3 infection, and 107 (4.4%) occurred in 78 patients with grade 4 infections. The median number of infections were 7 (IQR, 4-13) grade 1-2 infections, 3 (IQR, 2-6) grade 3 infections and 1 (IQR 1-1) grade 4 infection per patient, respectively, and the median number of days treated with in-hospital antimicrobials was 5 (IQR 2-9) days for grade 3 infections and 16 (7.5-25.0) days for grade 4 infections (P<0.0001). We demonstrated a steady increase in both grade 3 and 4 infections towards initiation of IgRT (Figure). During the last 6 months prior to IgRT initiation, we noticed a marked 2-fold increase for grade 3 infections and a 3-fold increase for grade 4 infections. After IgRT initiation, the proportion of patients with grade 3 and 4 infections decreased to levels similar to what was seen 2 to 4 years before IgRT initiation. The proportion of patients with grade 1-2 infections remained unchanged during IgRT. For comparison, IgRT untreated patients with hypogammaglobulinemia may likely inform whether the increase in grade 3 and 4 infections before IgRT follows the natural disease course or might be correlated to the IgRT indication itself. Summary/Conclusion: The proportion of patients with CLL/SLL requiring antimicrobial therapy for grade 3 and 4 infections decreased markedly after initiation of IgRT, whereas grade 1-2 infections remained largely unchanged.Keywords: Chronic lymphocytic leukemia, Immunoglobulin, Infection